Concomitant Chemoradiotherapy Research Articles

Hematologic Toxicity and Bone Marrow-Sparing Strategies in Chemoradiation for Locally Advanced Cervical Cancer: A Systematic Review

The standard treatment for locally advanced cervical cancer typically includes concomitant chemoradiation, a regimen known to induce severe hematologic toxicity (HT). Particularly, pelvic bone marrow dose exposure has been identified as a contributing factor to this hematologic toxicity. Chemotherapy further increases bone marrow suppression, often necessitating treatment interruptions or dose reductions. A systematic search for original articles published between 1 January 2006 and 7 January 2024 that reported on chemoradiotherapy for locally advanced cervical cancer and hematologic toxicities was conducted. Twenty-four articles comprising 1539 patients were included in the final analysis. HT of grade 2 and higher was observed across all studies and frequently exceeded 50%. When correlating active pelvic bone marrow and HT, significant correlations were found for volumes between 10 and 45 Gy and HT of grade 3 and higher. Several dose recommendations for pelvic bone and pelvic bone marrow sparing to reduce HT were established, including V10 < 90–95%, V20 < 65–86.6% and V40 < 22.8–40%. Applying dose constraints to the pelvic bone/bone marrow is a promising approach for reducing HT, and thus reliable implementation of therapy. However, prospective randomized controlled trials are needed to define precise dose constraints and optimize clinical strategies.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Impact of Human Papillomavirus (HPV) Infection on the Treatment Outcome of Concomitant Chemoradiotherapy (CRT) in Cervical Cancer

Background: Human Papilloma Virus (HPV) infection and its persistence are responsible for the development of cervical cancer (CaCx). Chemoradiotherapy (CRT) is the only treatment option, especially in advanced stages. However, it is not influenced by the status of HPV infection. CRT controls cancer growth along with mild to severe adverse effects. Objective: The aim of this study was to assess the HPV-associated risk factors and correlate them with chemoradiation therapy (CRT) response in cervical cancer. Methods: The study was undertaken in 103 histologically positive CaCx patients. Anthrodemographic and obstetric characterizations were conducted by face-to-face interviews, and HPV testing was done by conventional PCR. All the patients received a 40-50Gy total effective dose using tele‑ and brachytherapy. The treatment response, survivorship and statistical analysis were made using GraphPad Prism 9 and SPSS (ver.25.0). Results: Out of 103 patients, 84% were HPV infected, and 16% CaCx were HPV-negative. Advanced age, lower-middle socioeconomic status (SES), illiteracy, and patients from rural backgrounds were significantly higher in CaCx patients with HPV infection. Multiparity, irregular menstrual cycle, poor menstrual hygiene, and use of contraception were significantly associated with HPV positivity. Patients with HPV infection showed a better clinical response (P =0.031), alive vital status (P =0.007), and 59 months of median survival (P <0.001) with a poor hazard ratio (HR 0.29 at 95% CI). Conclusion: HPV-infected CaCx patients showed better response to definitive chemoradiation therapy compared to HPV-negative with a poor hazard ratio. Therefore, HPV testing can potentially stratify CaCx patients for more effective therapeutic regimens, treatment assessments and follow-ups.

Laryngeal Small Cell Neuroendocrine Carcinoma: Case Report and Literature Review

Neuroendocrine malignancy of the larynx are rare but represents the first nonsquamous tumor in this localization. The World Health Organization (WHO) classifies these tumors into 3 groups: typical carcinoid, atypical carcinoid tumor, and small cell neuroendocrine carcinoma (SmCC). SmCC have an aggressive natural history characterized by widespread metastasis. Treatment is based on concomitant or sequential chemoradiation. We report herein the case of a 69 years old men, who presented with laryngeal small cell neuroendocrine carcinoma revealed by progressive dysphonia and cervical lymphadenopathy. The diagnosis was confirmed by biopsy and histopathological study. Pre-treatment workup was negative for metastatic disease. He has received chemotherapy based on etoposide and cisplatin followed by chemoradiation. The evolution was marked by the development of metachronous lung metastasis. Unfortunately, the patient passed away during a chemotherapy-induced myelosuppression after the first palliative chemotherapy cure.

Exploring the impact of primary care utilization and health information exchange upon treatment patterns and clinical outcomes of glioblastoma patients.

There is limited literature describing care coordination for patients with glioblastoma (GBM). We aimed to investigate the impact of primary care and electronic health information exchange (HIE) between neurosurgeons, oncologists, and primary care providers (PCP) on GBM treatment patterns, postoperative outcomes, and survival. We identified adult GBM patients undergoing primary resection at our institution (2007-2020). HIE was defined as shared electronic medical information between PCPs, oncologists, and neurosurgeons. Multivariate logistic regression analyses were used to determine the effect of PCPs and HIE upon initiation and completion of adjuvant therapy. Kaplan-Meier and multivariate Cox regression models were used to evaluate overall survival (OS). Among 374 patients (mean age ± SD: 57.7 ± 13.5, 39.0% female), 81.0% had a PCP and 62.4% had electronic HIE. In multivariate analyses, having a PCP was associated with initiation (OR: 7.9, P < 0.001) and completion (OR: 4.4, P < 0.001) of 6 weeks of concomitant chemoradiation, as well as initiation (OR: 4.0, P < 0.001) and completion (OR: 3.0, P = 0.007) of 6 cycles of maintenance temozolomide thereafter. Having a PCP (median OS [95%CI]: 14.6[13.1-16.1] vs. 10.8[8.2-13.3] months, P = 0.005) and HIE (15.40[12.82-17.98] vs. 13.80[12.51-15.09] months, P = 0.029) were associated with improved OS relative to counterparts in Kaplan-Meier analysis and in multivariate Cox regression analysis (hazard ratio [HR] = 0.7, [95% CI] 0.5-1.0, P = 0.048). In multivariate analyses, chemoradiation (HR = 0.34, [95% CI] 0.2-0.7, P = 0.002) and maintenance temozolomide (HR = 0.5, 95%CI 0.3-0.8, P = 0.002) were associated with improved OS relative to counterparts. Effective care coordination between neurosurgeons, oncologists, and PCPs may offer a modifiable avenue to improve GBM outcomes.

Mucinous Differentiation in Colorectal Cancer: A 10-Year Experience Audit at King Faisal Specialist Hospital and Research Centre, Jeddah.

Given that colorectal canceris one of the leading causes of mortality, mucinous adenocarcinoma is one of the subtypes and is characterized by the presence of mucin-producing tumor cells with mucin components and is more challenging to manage. In Saudi Arabia, it represents approximately 10-15% of all colorectal carcinoma.The main etiological cause of mucinous adenocarcinoma is yet not well understood. The main goal of our study is to discuss the histopathology and the molecular background of mucinous colorectal adenocarcinoma and also to provide an update on its prognosis and therapeutics from recent published literature. It is a retrospective cohort study that wasconducted at King Faisal Specialist Hospital, Jeddah, Saudi Arabia. The study included 68 adult patients diagnosed with mucinous colon cancer, who did surgical resection alone or with or without adjuvant chemotherapy following from January 2011 to December 2020. The mucinous subtypes are found more commonly in the proximal colon. In our study, 26 patients (38.2% of the cases) were right-sided and 35 patients (51.5%) were from the left side, but these included the rectum as well and this reflects the higher incidence of diagnosis of rectal cancer in the region. Most tumors were classified as Grade II in 56 patients (82.4%), consistent with the intermediate differentiation status often associated with the mucinous subtypes. The most common symptom at presentation was abdominal pain in 38 patients(55.9%) followed by per rectal bleeding and abdominal mass. The management in our study was in line with the standard established practice and surgical resection as expected was the primary potentially curative approach. Notably of patients presenting with locally advanced rectal cancer, six patients underwent concomitant chemoradiotherapy followed by surgery and four patients had upfront surgery. The duration of the median follow-up was 32 months. At the time of analysis, 30 patients (44.1%) were alive and remained on regular follow-up, 17 patients (25%) had succumbed to the disease, and 21 patients (30.9%) were lost to follow-up. The median overall survival was not reached, and notably, 49 patients (71.6%)remained alive at the four-year mark. Whilst our study contributes to the current understanding of mucinous adenocarcinomas of the colon, further research in molecular profiling and genomic testing and larger clinical trials with tailored treatments is necessary to refine treatment strategies and improve outcomes.

Serum Pro-Inflammatory Cytokines and Leptin as Potential Biomarkers for Treatment Response and Toxicity in Locally Advanced Squamous Cell Carcinoma of the Head and Neck.

Squamous cell carcinoma of the head and neck (HNSCC) is a globally prevalent form of cancer with significant morbidity and mortality rates. The present study examines the relationship of serum pro-inflammatory cytokines and leptin levels with the effectiveness of therapy in individuals with HNSCC and their potential role as biomarkers for treatment response and toxicity. Induction chemotherapy and concomitant chemoradiotherapy were evaluated for efficacy and safety in 52 individuals with HNSCC. Both response and toxicity were evaluated, and serum levels of pro-inflammatory cytokines Interlukin-1 beta (IL-1β), Interlukin-2 (IL-2), Interlukin-6 (IL-6), and Tumor Necrosis Factor-Alpha (TNF-α) and leptin were measured using enzyme-linked immunoassay before and after treatment. Before treatment, these measurements were made in comparison with a control group with 50 healthy people. The results showed that serum cytokines and leptin levels varied depending on the response to treatment, with patients who had a complete or partial response (PR) showing significant decreases in IL-1 β, IL-6, and TNF-α levels and significant increases in IL-2 and leptin levels after treatment, with an improvement in cachexia. These results imply that variations in serum pro-inflammatory cytokines and leptin levels are likely related to the therapeutic effectiveness in HNSCC and may act as biomarkers for treatment response.

A RANDOMIZED STUDY ANALYZING CLINICAL AND DOSIMETRIC OUTCOME IN LOCALLY ADVANCED HEAD-AND-NECK CANCER TREATED WITH CONFORMAL CHEMORADIATION WITH OR WITHOUT INDUCTION CHEMOTHERAPY

Objective: Squamous cell carcinoma of the head and neck (HNSCC) represents around 10% of new cases in India annually and with a similar trend worldwide. Treatment strategies for stages III and IV HNSCC differ in view of resectability, organ preservation, and medical conditions. Induction chemotherapy (IC) followed by concomitant chemoradiation (CTRT) is widely practiced but Indian data regarding clinical outcomes in the IGRT scenario is still not promising. In this study, we tried to evaluate the dosimetric parameters, response rate, survival, and toxicities as well. Methods: We started our study in August 2019 with Institutional Ethical Committee approval with 42 patients in the CTRT arm and 40 patients in IC+CTRT arm. Patients in the CTRT arm received radiation (66–70 Gy) with 3 weekly cisplatin 80 mg/m2. In the induction arm, 2 cycles of taxane, platinum, 5FU were given followed by concomitant radiotherapy with the same dose and cisplatin. Results: Overall response rates (CR+PR) were 69% versus 72.5% (p=0.06). 2 years overall survival (OS) were 66.7% versus 69.5% (p=0.91). Median disease-free survival were slightly better in the IC+CTRT arm but mean OS was comparable. Mean values of clinical target volume, planning target volume, Spine Dmax, and parotid were lower in the induction arm (p&lt;0.05). Patients with IC experienced more hematological toxicities (p&lt;0.01). Conclusion: IC followed by CTRT offers better dosimetric outcome, slightly better progression-free survival, with more hematological toxicities and no OS benefit.

Treatment of poorly differentiated neuroendocrine carcinomas of rectum and anus with chemoradiotherapy: a single-centre evaluation

PurposePoorly differentiated neuroendocrine carcinoma (PDNEC) of the rectum and anus is a rare disease exhibiting aggressive biological behaviour, even if diagnosed early. Currently, there are no agreed standard treatment approaches and management of locally advanced (LA) and metastatic PDNEC usually follows treatments used in pulmonary neuroendocrine carcinomas because of the similarities with small cell lung cancer. The role of surgery in PDNEC is still debated and the benefit of chemoradiotherapy (CRT) is unknown. This report summarises the experiences of CRT application in anorectal PDNEC in a single Danish institution.MethodsAll patients with PDNEC treated with concomitant CRT between May 2019 and January 2021 at a University hospital in Denmark were evaluated. Demographics, treatment and survival outcomes were collected and analysed.ResultsSix patients were identified. Five patients received radiotherapy with 50.4 Gy/28 fractions, and four were eligible for curative resection after the CRT. Distant metastasis was observed in four patients at diagnosis. Two patients with synchronous liver metastases were treated with RFA, and one received a liver resection. The treatment was well tolerated with limited side effects. The median follow-up time was 17 months (range 10–36 months), and the median duration of response was 11.2 months (range 8.1 to 24.2 months). One patient achieved a complete response.ConclusionA multimodal treatment approach with CRT in advanced stages of PDNEC in a highly selected patient group is well tolerated and with a high chance of achieving local control and, combined with surgery, even complete response in a single case.

Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase II trial.

Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma. This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m2 of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ (150-200 mg/m2 × 5 d during each 28-d cycle) plus anlotinib (8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Thirty-three patients received the planned treatment. The median PFS was 10.9 months (95% CI, 9.9-18.7 months) and the 12-month PFS rate was 48.5%. The median OS was 17.4 months (95% CI, 14.5-21.1 months) and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58% (n = 19)], hypoalbuminemia [46% (n = 15)], and hypercholesterolemia [46% (n = 15)] during concurrent chemoradiotherapy and leukopenia [73% (n = 24)], hypertriglyceridemia [67% (n = 22)], and neutropenia [52% (n = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1 (HR, 5.6; 95% CI, 1.3-23.7; P = 0.021) and RP1L1 alterations (HR, 11.1; 95% CI, 2.2-57.2; P = 0.004) were associated with a significantly shorter PFS. Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

214 Assessment of patient's quality of life after total laryngectomy vs. concomitant chemoradiotherapy for laryngeal preservation

214 Assessment of patient's quality of life after total laryngectomy vs. concomitant chemoradiotherapy for laryngeal preservation

Single Nucleotide Polymorphisms as Biomarker Predictors of Oral Mucositis Severity in Head and Neck Cancer Patients Submitted to Combined Radiation Therapy and Chemotherapy: A Systematic Review.

Single Nucleotide Polymorphisms (SNPs) are the most common type of genetic variation found in an individual's DNA sequences. SNPs can occur in both coding and non-coding regions of the genome and can affect gene expression, protein function, and disease susceptibility. In this systematic review, we evaluate the potential of SNPs as biomarkers in the assessment of oral mucositis (OM) severity in head and neck cancer (HNC) patients treated with concomitant chemoradiation (CRT). The study selection process involved screening 66 articles from different platforms, and after removing duplicates and excluding articles that did not meet the eligibility criteria, 23 articles were included for full-text evaluation. Among them, genes from several pathways were analyzed. The DNA damage repair pathways had the highest number of genes studied. The most frequently analyzed gene was XRCC1. The proinflammatory cytokine pathways evaluated were TNF, with three articles, and NF-κB, with one article. Most included studies showed a potential association between certain SNPs and high-grade mucositis. We conclude that SNPs can be used as possible biomarkers for the assessment of OM intensity in HNC patients, and further research is needed to explore the potential of SNPs in personalized medicine for HNC treatment.

Evaluation of the toxicity of prophylactic extended-field radiation therapy with volumetric modulated arc therapy in combination with concomitant chemoradiotherapy in patients with locally advanced stage IIIC1r cervical cancer according to the 2018 FIGO classification

Evaluation of the toxicity of prophylactic extended-field radiation therapy with volumetric modulated arc therapy in combination with concomitant chemoradiotherapy in patients with locally advanced stage IIIC1r cervical cancer according to the 2018 FIGO classification

Induction chemotherapy plus concomitant oxaliplatin-based chemoradiotherapy for locally advanced rectal cancer: A real world experience at San Raffaele Hospital.

144 Background: The standard treatment of locally advanced rectal cancer (LARC) consists of giving preoperative chemoradiation therapy (CT/RT) followed by surgery. Recently, total neoadjuvant therapy (TNT) has shown greater efficacy in terms of increasing the rate of complete pathological response (pCR) and reducing local and systemic relapse. However, based on the proposed therapy scheme, the risk of overtreatment and side effects is not negligible. The objective of this study was to evaluate the efficacy and safety of neoadjuvant doublet with oxaliplatin-based CT and concomitant RT. Methods: Patients with clinically staged II-III rectal cancer were treated with preoperative CT/RT using up to 3 cycles of oxaliplatin and fluoropyrimidine plus pelvic radiation daily, for a total dose of 46.2 Gy in 18 fractions. The first cycle of mXELOX (oxaliplatin 85 mg/m2 D1 Q14 plus capecitabine 825 mg/m2 BID) was administrated before RT (as induction CT); the other 2 cycles of mXELOX were administrated concurrent with RT, with capecitabine continued until the end of RT. Radical resection was performed within median 11 weeks of the last dose of RT. Adjuvant CT with FOLFOX or XELOX was administered according to pathological report. Results: Between 2007 and 2022, a total of 186 patients were enrolled, mean age was 61 years. 19 (10.2%) patients were clinically stage II and 167 (89.8%) were clinically stage III. Any grade most common toxicities during neoadjuvant CT/RT included diarrhea (53.2%), proctitis (51.2%) and neutropenia (14.5%). The most common grade 3/4 toxicity was diarrhea (9.1%). A total of 146 (78.5%) patients achieved a downstaging after CT/RT and 174 (93.5%) patients underwent surgery with R0 resection. Clinical meaningful surgical morbidities included infections (10.7%), anastomotic fistula (10.2%) and anastomotic leakage (7.5%). The pathological complete response (pCR) rate was 25.3%. Adjuvant CT was administered in 122 (65.6%) patients. Local recurrences and distant metastases were confirmed in 6 (3.2%) and 54 (29%) cases respectively. Median observation time, calculated with reverse Kaplan-Meier estimator, was 84 months and median overall survival (OS) was not reached. The estimated probability of OS (Kaplan-Meier method) at 3-5 years were 92.8% and 85.5% respectively. The median disease-free survival (DFS) was not reached and the estimated probability of DFS at 3-5 years were 74.7% and 69% respectively. Conclusions: Considering the low rate of toxicities and the comparable efficacy in terms of downstaging, pCR, probability of DFS and OS to other TNT regimens proposed in recent studies, our schedule of neoadjuvant CT/RT may represent a potential alternative to standard CT/RT in selected patients with LARC.

Overall survival, disease-free survival and quality of life in patients affected by HPV mediated p16+ oropharyngeal squamous cell carcinoma treated with upfront trans-oral robotic surgery vs radiotherapy or chemoradiotherapy.

Treatment de-intensification for p16 + oropharyngeal squamous cell carcinoma (OPSCC) is an area of active research to reduce the side effects and improve patients' quality of life (QoL). In this paper we evaluated the Overall Survival (OS), the Disease-Free Survival (DFS) and the QoL of patients affected by p16 + OPSCC according to their prognostic stage group (PSG) and different treatments. Patients were selected retrospectively through our Electronic Tumor Board Database according to prespecified inclusion criteria. Basic data of eligible patients were recorded and analyzed. Then, OS and DFS were evaluated according to the PSG and the treatments performed. Patients alive completed three questionnaires: the QoL Questionnaire Core 30 (QLQ-C30), the QoL Questionnaire Head & Neck 43 (QLQ-HN43) and the MD Anderson Dysphagia Inventory (MDADI) questionnaire. Sixty-one patients were included in this study. Eight patients died from the disease and the remaining 53 patients completed the 3 questionnaires. Fifteen (25%) patients were treated with upfront surgery, 6 (10%) patients with definitive radiotherapy and 40 (65%) patients with concomitant chemoradiotherapy. Comparing the DFS and the OS of PSG I patients by the different treatments performed, no statistically significant difference was identified. Patients treated with upfront surgery showed better outcomes in some aspects of their QoL. For p16 + OPSCC PSG I patients, upfront surgery can be considered a valid alternative to radiotherapy or chemoradiotherapy while maintaining a comparable DFS and OS and giving patients better results in terms of specific aspects of their QoL.

Compare Two Different Fractionated Regimes of HDR Intracavitary Brachytherapy after Concomitant Chemoradiation in Carcinoma Cervix: A Prospective Study

Background: Cervical cancer is the common cancer cause of death among women in developing countries. High Dose Rate (HDR) intracavitary brachytherapy that is given with or sequential after EBRT, is an integral component in the treatment of carcinoma of the cervix. In recent years, High Dose Rate (HDR) brachytherapy in combination with External Beam Radiotherapy (EBRT) has been popular in the management of carcinoma of the cervix. Objectives: To evaluate treatment response post 3 and 6 months after treatment completion and treatment-related toxicities during treatment in weekly v/s biweekly HDR intracavitary brachytherapy after concomitant chemoradiation in squamous cell carcinoma cervix patients. Methods: A total of 60 cervical cancer patients fulfilling the inclusion criteria were selected. Patients were randomly assigned to the weekly and Biweekly HDR ICBT using the chit-box method with replacement. Arm A (Study arm): 30 patients with concurrent EBRT (50 Gy/25 fractions with 2 Gy per fraction) with weekly cisplatin (35 mg/m2) followed by HDR-ICBT 5 Gy * 5 fractions biweekly after completion of EBRT. Arm B (Control arm): 30 patients with concurrent EBRT (50 Gy/25 fractions with 2 Gy per fraction) with weekly cisplatin (35 mg/ m2) followed by HDR - ICBT 7.5 Gy * 3 fractions weekly after completion of EBRT. Results: Patients were assessed at 3 and 6 months to determine the local disease response and the incidence of any toxicities assessed during the treatment. All responses were graded as either CR (complete response), PR (partial response), SD (stable disease), or PD (progressive disease). 30 patients were assessed for therapy response using the WHO criteria. At 3 months arm A showed 86% CR and arm B showed 90% CR. 2 patients in arm A and 1 patient in arm B had PR. In both arms 2 patients had progressive disease. At 6 months 1 patient in both arms who had progressive disease converted into partial response after taking post RT chemotherapy. Conclusions: To sum up, brachytherapy is a vital aspect of the process of treating cervical cancer. Several centers have experimented with various doses and fractionation regimes. Patients in the current trial reported no safety concerns or intolerability issues across any treatment protocol. Arm A had treatment completion before arm B with comparable disease response and toxicities. Therefore, the choice of treatment plan depends on the individual patient’s circumstances and the institution’s demands. nonetheless, longer follow-ups and a bigger patient sample are needed for a solid evaluation of disease response and toxicity.

Interaction of low-energy electrons with radiosensitizers.

We provide an experimentalist's perspective on the present state-of-the-art in the studies of low-energy electron interactions with common radiosensitizers, including compounds used in combined chemo-radiation therapy and their model systems. Low-energy electrons are important secondary species formed during the interaction of ionizing radiation with matter. Their role in the radiation chemistry of living organisms has become an important topic for more than 20 years. With the increasing number of works and reviews in the field, we would like to focus here on a very narrow area of compounds that have been shown to have radio-sensitizing properties on the one hand, and high reactivity towards low-energy electrons on the other hand. Gas phase experiments studying electron attachment to isolated molecules and environmental effects on reaction dynamics are reviewed for modified DNA components, nitroimidazoles, and organometallics. In the end, we provide a perspective on the future directions that may be important for transferring the fundamental knowledge about the processes induced by low-energy electrons into practice in the field of rational design of agents for concomitant chemo-radiation therapy.

Pd-L1 Evaluation in Serum and Tumoral Circulating Extracellular Vescicles in Locally Advanced Nsclc After Concomitant Chemoradiation: A Surrogate of Tumor Microenviroment Change from Cold Tumor to Hot Tumor

Background: Pacific trial has revolutioned the outcome and the approach in locally advanced (LA) unresectable Non Small Cell Lung Cancer (NSCLC). In 2018 the European Medicine Agency (EMA) approved the use of Durvalumab only in adults whose tumours on biopsy specimen expresses PD-L1 on ≥ 1% of tumour cells despite this cut-off was not provided by the original randomised study. In vitro and in vivo studies have recorded the up regulation of PD-L1 expression in the tumor microenviroment (TME) after chemoradiation regrdless the expression on biopsy. Liquid biopsy could be helpful in detection of circulating PD-L1 in this set. Aim of this observational multicentre prospective study is to assess on liquid biopsy the up-regulation of PD-L1on serum and tumoral circulating extracellular vescicles (cEVS) from patients with LA NSCLC not expressing the PD-L1 on biopsy and treated with concurrent chemoradiation (CCRT). Methods: Locally advanced NSCLC PD-L1 &lt; 1 % biopsy proven will be enrolled in this study. A blood sample will be taken the day before (T0), 14 days after CCRT (T1) and 1 months later (T2). Patients will be treated with CCRT with platinum-based doublet and 60-66 Gy total radiation dose. Soluble PD-L1 will be analysed by ELISA. PD-L1on cEVs will be isolated from serum and phenotyped by nanoparticle tracking analysis, microscopy and flow cytometry. The statistical significant improvement in PD-L1 expression in serum and cEVs at T0 -T1-T2 will be assessed by t-test for p= 0.05; for multiple test p-value will be corrected with FDR.

Metabolomic Insight into Implications of Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Locally Advanced Head and Neck Cancer.

The present study compares two groups of locally advanced patients with head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (cCHRT), specifically those for whom it is a first-line treatment and those who have previously received induction chemotherapy (iCHT). The crucial question is whether iCHT is a serious burden during subsequent treatment for LA-HNSCC and how iCHT affects the tolerance to cCHRT. Of the 107 LA-HNSCC patients, 54 received cisplatin-based iCHT prior to cCHRT. The patients were clinically monitored at weekly intervals from the day before until the completion of the cCHRT. The 843 blood samples were collected and divided into two aliquots: for laboratory blood tests and for nuclear magnetic resonance (NMR) spectroscopy (a Bruker 400 MHz spectrometer). The NMR metabolites and the clinical parameters from the laboratory blood tests were analyzed using orthogonal partial least squares analysis (OPLS) and the Mann-Whitney U test (MWU). After iCHT, the patients begin cCHRT with significantly (MWU p-value < 0.05) elevated blood serum lipids, betaine, glycine, phosphocholine, and reticulocyte count, as well as significantly lowered NMR inflammatory markers, serine, hematocrit, neutrophile, monocyte, red blood cells, hemoglobin, and CRP. During cCHRT, a significant increase in albumin and psychological distress was observed, as well as a significant decrease in platelet, N-acetyl-cysteine, tyrosine, and phenylalanine, in patients who received iCHT. Importantly, all clinical symptoms (except the decreased platelets) and most metabolic alterations (except for betaine, serine, tyrosine, glucose, and phosphocholine) resolve until the completion of cCHRT. In conclusion, iCHT results in hematological toxicity, altered lipids, and one-carbon metabolism, as well as downregulated inflammation, as observed at the beginning and during cCHRT. However, these complications are temporary, and most of them resolve at the end of the treatment. This suggests that iCHT prior to cCHRT does not pose a significant burden and should be considered as a safe treatment option for LA-HNSCC.

The Role of c-MET as a Biomarker in Patients with Bladder Cancer Treated with Radical Chemo-Radiotherapy.

Bladder cancer is a highly aggressive cancer, and muscle invasive urothelial carcinoma (MIUC) requires aggressive strategy. Concomitant chemo-radiotherapy (CRT) appears as a therapeutic option that allows bladder sparing. No biomarker is currently available to optimally select patients for CRT. We retrospectively enrolled patients with MIUC who were treated in a curative setting with CRT. Based on c-MET expression in pre-treatment tumor tissue, patients were stratified into two groups: no expression of c-MET (group A) and expression of c-MET (group B). We evaluated the outcome of these patients based on c-MET expression. After a median follow-up of 40 months, 13 patients were enrolled in this analysis, 8 in group A and 5 in group B. The disease recurrence was 25% in group A and 100% in group B. Compared to group A, patients from group B experienced more frequent and more rapid recurrence in terms of metastases; the 3-year metastatic recurrence rate was 13% and 100%, respectively. The c-MET expression was also associated with a higher rate of cancer-related deaths. In this retrospective analysis, c-MET expression was associated with worse disease-free survival and survival in patients treated radically with CRT.